Clonal variation of tumor cell escape due to genetic and epigenetic instability
Clone no. . | Postinsertional recombination . | Chromosomal deletion and/or chromosomal loss . | Gene silencing . | Vector integration site . | Next flanking genes (start of transcription) . |
|---|---|---|---|---|---|
| 1 | ND (< 2.3 × 10-8) | 8.2 × 10-5 | ND (< 2.3 × 10-8) | Chromosome 6 (B3; start 49122055 bp, end 49122282 bp) | AI854703 (49074600 bp); NM_174960 (49122891 bp) |
| 2 | 2.9 × 10-2 | 6.4 × 10-3 | ND (< 2.0 × 10-8) | Chromosome 3 (H2; start 141965299 bp, end 141965563 bp) | Dapp1 (141855603 bp); NM_177860 (141972963 bp) |
| 3 | 3.2 × 10-3 | 8.3 × 10-3 | ND(< 4.7 × 10-8) | Chromosome 13 (D2.1; start 107923565 bp, end 107924277 bp) | 9630011N22Rik (107807963 bp); Pde4d (108438579 bp) |
| 4 | ND (< 2.9 × 10-8) | ND (< 2.9 × 10-8) | 8.9 × 10-2 | Chromosome 11 (E2; start 120811840 bp, end 120811863 bp) | 4430402O11Rik (120790163 bp); 1110054H05Rik (120849830 bp) |
| 5 | 1.8 × 10-5 | ND (< 8.1 × 10-9) | ND (< 8.1 × 10-9) | Chromosome 1 (E3; start 129935602 bp, end 129935674 bp) | D130011D22Rik (129221654 bp); Mgat5 (130003677 bp) |
| 6 | ND (< 6.3 × 10-8) | 2.4 × 10-3 | ND (< 6.3 × 10-8) | Chromosome 6 (B2; start 47840185 bp, end 47840326 bp) | Cull (47797245 bp); Ezh2 (47842412 bp) |
Clone no. . | Postinsertional recombination . | Chromosomal deletion and/or chromosomal loss . | Gene silencing . | Vector integration site . | Next flanking genes (start of transcription) . |
|---|---|---|---|---|---|
| 1 | ND (< 2.3 × 10-8) | 8.2 × 10-5 | ND (< 2.3 × 10-8) | Chromosome 6 (B3; start 49122055 bp, end 49122282 bp) | AI854703 (49074600 bp); NM_174960 (49122891 bp) |
| 2 | 2.9 × 10-2 | 6.4 × 10-3 | ND (< 2.0 × 10-8) | Chromosome 3 (H2; start 141965299 bp, end 141965563 bp) | Dapp1 (141855603 bp); NM_177860 (141972963 bp) |
| 3 | 3.2 × 10-3 | 8.3 × 10-3 | ND(< 4.7 × 10-8) | Chromosome 13 (D2.1; start 107923565 bp, end 107924277 bp) | 9630011N22Rik (107807963 bp); Pde4d (108438579 bp) |
| 4 | ND (< 2.9 × 10-8) | ND (< 2.9 × 10-8) | 8.9 × 10-2 | Chromosome 11 (E2; start 120811840 bp, end 120811863 bp) | 4430402O11Rik (120790163 bp); 1110054H05Rik (120849830 bp) |
| 5 | 1.8 × 10-5 | ND (< 8.1 × 10-9) | ND (< 8.1 × 10-9) | Chromosome 1 (E3; start 129935602 bp, end 129935674 bp) | D130011D22Rik (129221654 bp); Mgat5 (130003677 bp) |
| 6 | ND (< 6.3 × 10-8) | 2.4 × 10-3 | ND (< 6.3 × 10-8) | Chromosome 6 (B2; start 47840185 bp, end 47840326 bp) | Cull (47797245 bp); Ezh2 (47842412 bp) |
Frequency values are the ratio of the calculated number of initial GCV-resistant cells (based on the size and latency of the relapsed tumor) to the total number of tumor cells at the onset of GCV therapy (“Materials and methods”). The localisations of the vector insertion sites were mapped with reference to the ENSEMBL database25 using the BlastSearch function. Next flanking genes with respect to the insertion site contain those which are ENSEMBL-predicted and known. ND indicates not detectable. In the “Vector integration site” column, the information in parentheses describes the chromosomal region and the matching sequences.